Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons

Abstract

The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons.

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

“…1). When Ki67, DCX and pyknotic cell numbers were standardized to percentages of the mean values of the control animals, the runninginduced increase in the number of DCX-positive cells was significantly higher than the increase in the number of Ki67-positive cells (t (11) =3.06, p=0.010). Both standardized DCX (t (11) =4.67, p=0.001) and Ki67 (t (11) =2.61, p=0.024) values were significantly larger than the standardized value of pyknotic cells.…”

“…1). The mean individual increase relative to the first week of the rewarded runners was 78% (t (11) =2.94, p=0.013), whereas the controls showed a smaller but significant increase of 7% (t (11) =3.03, p=0.012).…”

“…Within the rewarded running group an increase of performance could be observed on day eight of the experiment (t (11) =-4.19, p=0.002), i.e. the first day of rewarded running, whereas the non-rewarded runners showed a slight and marginally significant decrease in the average performance compared to the day before (t (11) =2.17, p=0.053; Fig. 3).…”

“…Changes in the extent of adult hippocampal neurogenesis are associated with changes in the performance of animals in hippocampus-dependent behavioral tasks [7][8][9][10][11], and a recent study of conditional TLX knockout mice, a gene expressed by adult neural stem cells, suggest a causal link between the performance in specific aspects of behavioral tasks and neurogenesis [12]. Voluntary physical exercise is a consistent and strong modulator of adult hippocampal neurogenesis.…”

Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus

“…This phenomenon has received widespread attention because of its perceived role in functions such as learning, memory, and mood (Aimone et al 2006;Clelland et al 2009;Drapeau et al 2003;Dupret et al 2007;Eisch et al 2008;Imayoshi et al 2008;Jessberger et al 2009;Kee et al 2007;Kuhn et al 1996;Leuner et al 2006;Sahay and Hen 2007;Santarelli et al 2003). However, the extent of neurogenesis progressively declines with age resulting in~90 % decline in old age (Kuhn et al 1996;Rao et al 2005Rao et al , 2006.…”